Description of the product: EchiTAb-Plus-ICP is a preparation made of horse immunoglobulins used for the treatment of envenomings by Sub-Saharan African snakes of the family Viperidae (genera Echis and Bitis) and of spitting cobras of the family Elapidae (Naja sp). It is not effective for the treatment of envenomings by neurotoxic elapid venoms such as those from neurotoxic cobras (Naja sp) and mambas (Dendroaspis sp). Each vial of 10 milliliters of antivenom neutralizes 30 mg of the venom of Echis ocellatus, 20 mg of the venom of Bitis arietans, and 2 mg of the venom of Naja nigricollis. It is also effective in the neutralization of venoms of the viperids Echis pyramidum laekeyi, Echis leucogaster, Bitis gabonica, Bitis rhinoceros, Bitis nasicornis, and of the spitting cobras Naja mossambica and Naja pallida. EchiTAb-Plus-ICP is manufactured as a liquid preparation. It has to be stored at 2-8 °C. The shelf-life of the product is 3 years. Before administration, the product should be visually inspected; in case of turbidity, it should not be used.

Treatment of snakebite envenomings with EchiTAB-Plus-ICP

Treatment in health care facilities

Antivenom should be administered only to patients presenting systemic or severe local manifestations of envenoming. Envenomings by viperid species of the genus Echis are characterized by local swelling and necrosis, and by systemic manifestations such as hemorrhage, coagulopathy and cardiovascular disturbances. Envenomings by viperid species of the genus Bitis are characterized by local swelling and necrosis, and by systemic manifestations such as hemorrhage and cardiovascular disturbances. In turn, envenomings by spitting cobras (Naja sp) are characterized by prominent local tissue damage, i.e. edema, subcutaneous necrosis, without bleeding and coagulopathy. Many snakebites are not associated with envenomings and, therefore, antivenom should be administered only when objective signs of envenoming are observed. The initial dose of EchiTAb-Plus-ICP antivenom should be 4 vials of 10 mL. This dose should be used both in adults and children alike.

Testing for possible hypersensitivity to antivenom (by intradermal or conjunctival tests) should not be performed in health care facilities, as they have a very poor predictive value in horse-derived antivenoms, because the majority of early adverse reactions in these cases are not true IgE-dependent anaphylactic reactions but instead de novo reactions which do not depend on IgE.

Antivenom administration should be performed by the intravenous (i.v.) route by qualified personnel. It can be administered by i.v. bolus at a rate of about 5 mL per minute or diluted in isotonic saline solution and infused in 60 minutes.

When antivenom is administered diluted in saline solution, an i.v. route should be cannulated and the complete dose of antivenom to be applied has to be diluted in 500 mL saline solution (in adults) or 200 mL saline solution (in children to avoid a fluid overload). Antivenom is then infused, initially at a low flow to observe possible early adverse reactions which develop within the first 20 min of infusion (see below).

If no early adverse reactions occur in 20 min, then increase the flow of antivenom infusion in order to administer the whole dose in 60 min. If there are evidences of early adverse reactions (urticarial, pruritus, bronchospasm, hypotension, angioedema), antivenom infusion should be suspended and the patient should receive a combination of adrenaline (epinephrine) 0.1% (1:1000) subcutaneously at a dose of 0.5-1.0 mL for adults or 0.01 mg/kg for children. In addition, i.v. administration of an antihistamine (chlorpheniramine maleate or promethazine) and steroids. Once the adverse reaction has been controlled, the antivenom infusion should be restarted.

If the antivenom treatment is successful, the main manifestations of envenoming should be halted within the first hours of treatment. In the case of envenomings inflicted by viperids, bleeding should stop within 3 hours of the start of antivenom infusion, and clotting disturbances (i.e. 20 min whole blood clotting time) should be corrected within 12 hours in all treated patients. If bleeding or coagulopathy persist at 12 hours, an additional dose of 4 vials of 10 mL should be administered i.v., as described above. Likewise, in the event of ‘recurrence’ of envenoming, i.e. when signs and symptoms of envenoming reappear after initial control of signs and symptoms of envenoming by antivenom treatment, an additional dose of 4 vials of 10 mL should be administered.

Late reactions to antivenom administration (serum sickness) might occur 5-20 days after treatment. It is characterized by itcnhing, urticarial, fever, arthralgia and proteinuria. Patients should be informed on this possibility. This reaction is treated with antihistamines and steroids (e.g. prednisolone).

When i.v. administration of antivenom is not possible, it can be injected by the intramuscular (i.m.) route, although this is less effective, as the absorption of antivenom antibodies is slow and bioavailability is reduced. In these cases, administration of antivenom should be performed by deep intramuscular injection at multiple sites in the anterior and lateral aspects of the thighs, followed by massage to facilitate absorption. Treatment of any early adverse reaction should be performed as described above.

Ancillary treatment

Tetanus prophylaxis: Routine administration of tetanus toxoid should be performed in snakebitten patients.

Infection of the wound: Infection might occur in snakebitten patients owing to the presence of a rich microbial flora in the venom, together with local necrosis which facilitates infection. In case of local tissue necrosis or evidence suggesting infection (such as hot reddened local swelling), antibiotics should be administered. A combination of penicilliln (or clindamycin) plus a broad spectrum antibiotic (such as an aminoglucoside) should be considered.

Care of the bitten limb and debridement of necrotic tissue: The bitten region should be cleaned with antiseptics. Necrotic tissue should be debrided to avoid further necrosis and infection. Likewise, abscesses should be drained and pus should be cultured, when possible for identification of bacteria and selection of the most appropriate antibiotic.

Surgical decompression: The development of compartmental syndrome should be ideally diagnosed by measuring intracompartmental pressure with a manometer. When pressures are over 45 mm Hg, surgical decompression, i.e. fasciotomy, has to be considered. Care should be taken as to ensure that a compartmental syndrome is actually developing.

Treatment of hypotension and shock: The key intervention to halt cardiovascular disturbances is administration of antivenom. If patients have had extensive blood loss, administration of a plasma expander is necessary. When hematological parameters are affected, transfusion should be considered.

Treatment of renal alterations: Acute kidney injury may occur in envenomings by viperid snakes. Thus, monitoring of urine volume, together with laboratory analysis of serum creatinine levels and urinary sediment, should be performed. If the urinary volume decreases below 400 mL in 24 hours, the patient should receive a fluid therapy (isotonic fluid), with monitoring of the central venous pressure to avoid fluid overload. Furosemide and dopamine should be considered to restore renal function. In cases where no response is obtained, the possibility of dialysis has to be considered.